A primary monolayer culture system of differentiated fetal rat hepatocytes is being used to analyze humoral mechanisms controlling hepatocellular growth. In combination with animal studies (partially hepatectomized adult rats), a picture of complex but highly integrated endocrine control along with growth-associated hepatic plasma membrane changes has emerged. The diversity of hormonal requirements suggests that control occurs at many cellular levels not all of which operate through cyclic nucleotide mediators. The in vivo existence of heterogeneous Go-populations (the physical basis of which may reside in differing sets of steady-state equilibrium interactions between cell receptors and hormones) is hypothesized to result from positional information in the form of humoral factor gradients radiating from the portal triad towards the central vein.